Abstract：
Fibre-based oral drug delivery systems are an attractive approach to addressing low drug solubility, although clear strategies for incorporating such systems into viable dosage forms have not yet been demonstrated. The present study extends our previous work on drug-loaded sucrose microfibres produced by centrifugal melt spinning to examine systems with high drug loading and investigates their incorporation into realistic tablet formulations. Itraconazole, a model BCS Class II hydrophobic drug, was incorporated into sucrose microfibres at 10, 20, 30, and 50% w/w. Microfibres were exposed to high relative humidity conditions (25 °C/75% RH) for 30 days to deliberately induce sucrose recrystallisation and collapse of the fibrous structure into powdery particles. The collapsed particles were successfully processed into pharmaceutically acceptable tablets using a dry mixing and direct compression approach. The dissolution advantage of the fresh microfibres was maintained and even enhanced after humidity treatment for drug loadings up to 30% w/w and, importantly, retained after compression into tablets. Variations in excipient content and compression force allowed manipulation of the disintegration rate and drug content of the tablets. This then permitted control of the rate of supersaturation generation, allowing the optimisation of the formulation in terms of its dissolution profile. In conclusion, the microfibre-tablet approach has been shown to be a viable method for formulating poorly soluble BCS Class II drugs with improved dissolution performance.
摘要：
基于纤维的口服药物递送系统是解决低药物溶解度的有吸引力的方法。尽管尚未证明将此类系统纳入可行剂型的明确策略。本研究扩展了我们先前通过离心熔体纺丝生产的载药蔗糖微纤维的工作，以检查具有高载药量的系统，并研究将其掺入实际的片剂配方中。伊曲康唑,一种BCSII类疏水药物模型，以10、20、30和50％w/w掺入蔗糖微纤维中。将微纤维暴露于高相对湿度条件（25°C/75％RH）30天，以故意诱导蔗糖重结晶并使纤维结构塌陷成粉状颗粒。使用干混合和直接压缩方法将塌陷的颗粒成功地加工成药学上可接受的片剂。对于高达30％w/w的药物负载，在湿度处理后，新鲜微纤维的溶解优势得以保持甚至增强，重要的是,压制成片剂后保留。赋形剂含量和压缩力的变化允许操纵片剂的崩解速率和药物含量。然后，这允许控制过饱和生成的速率，允许在其溶出曲线方面优化制剂。总之,微纤维-片剂方法已被证明是配制具有改善的溶出性能的难溶性BCSII类药物的可行方法。
